Affiliations: [a] Neuroscience Research Australia, Sydney, Australia
| [b]
ARC Centre of Excellence in Cognition and its Disorders, Sydney, Australia
| [c] School of Medical Sciences, The University of New South Wales, Sydney, Australia
| [d] Department of Molecular Genetics, VIB, Antwerp, Belgium
| [e] Institute Born-Bunge, University of Antwerp, Antwerp, Belgium
| [f] Faculty of Health Sciences, The University of Sydney, Sydney, Australia
| [g] Department of Neurology, Massachusetts General Hospital, Charlestown, USA
Correspondence:
[*]
Correspondence to: Dr. Tim Van Langenhove, Neuroscience Research Australia, Margarete Ainsworth Building, Barker Street (PO Box 1165), Randwick NSW 2031, Australia. Tel.: +61 2 9399 1134; Fax: +61 2 9399 1047; E-mail: tim.vanlangenhove@gmail.com.
Abstract: Background: A proportion of patients with frontotemporal dementia (FTD) also develop amyotrophic lateral sclerosis (ALS). Objective: We aimed to establish the risk of developing ALS in patients presenting with FTD and to identify the relevant clinical variables associated with progression from FTD to FTD-ALS. Methods: Of 218 consecutive patients with FTD, 10.1% had a dual FTD-ALS diagnosis at presentation. The remaining 152 FTD patients with follow-up of at least 12 months were included in the present study. We calculated the rate of progression to FTD-ALS and compared the baseline characteristics of FTD patients who developed ALS to those who did not develop ALS. Results: Five percent of FTD patients developed ALS. The incidence rate of ALS was 6.7/100 patient-years in patients with FTD symptoms since 1 year, which declined with duration of FTD symptoms. No FTD patients developed ALS after 5 years. Five out of 8 FTD patients who developed ALS had presented with a mixed behavioral variant FTD and progressive non-fluent aphasia (bvFTD+PNFA) phenotype, 2 with bvFTD, and 1 with PNFA. Progression to FTD-ALS was significantly more frequent in patients with bvFTD+PNFA compared to those without this phenotype (p < 0.0001, OR 38.3, 95% CI: 7.3 to 199.2), and in FTD patients who carried the C9orf72 repeat expansion compared to those without the repeat expansion (p = 0.02, OR 8.0, 95% CI: 1.7 to 38.6). Conclusions: FTD patients with a mixed bvFTD+PNFA phenotype and with a C9orf72 repeat expansion should be closely monitored for the possible development of ALS. The risk of developing ALS in FTD appears to decline with the duration of FTD symptoms.
